From HPV to COVID-19 and beyond: leveraging the power of serology and standards
Authors: Heidi A Hempel, Troy J Kemp, Nancy Roche, Ligia A Pinto
Journal: The Lancet Microbe (2023)

The COVID-19 pandemic highlighted the need for infrastructure to respond to public health emergencies and regulate associated commercial assay development. During the COVID-19 emergency, biomedical laboratories and test developers rapidly developed serology assays for SARS-CoV-2 antibodies, with varied and often inadequate performance.1Pinto LA Shawar RM O'Leary B et al.A trans-governmental collaboration to independently evaluate SARS-CoV-2 serology assays.Microbiol Spectr. 2022; 10e0156421Crossref Scopus (7) Google Scholar, 2Shuren J Stenzel T The FDA's experience with Covid-19 antibody tests.N Engl J Med. 2021; 384: 592-594Crossref PubMed Scopus (19) Google Scholar In April, 2020, a trans-governmental network, including the Food and Drug Administration (FDA), National Cancer Institute (NCI), Centers for Disease Control and Prevention, Biomedical Advanced Research and Development Authority, and Frederick National Laboratory for Cancer Research (FNLCR), was established to independently evaluate commercial SARS-CoV-2 serology assays to inform FDA regulatory decisions on emergency use authorisation suitability.1Pinto LA Shawar RM O'Leary B et al.A trans-governmental collaboration to independently evaluate SARS-CoV-2 serology assays.Microbiol Spectr. 2022; 10e0156421Crossref Scopus (7) Google Scholar As a human papillomavirus (HPV) reference serology laboratory, the HPV Serology Laboratory (HPVSL) at FNLCR has been leading an international standardisation initiative since 2017, and has been working closely with the National Institute of Biological Standards and Control and WHO to build serology standards (appendix). The HPVSL is sponsored by NCI and the Bill & Melinda Gates Foundation and has developed and validated laboratory markers of protection and monitored immunity in clinical and preclinical studies.3Baisley K Kemp TJ Kreimer AR et al.Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose of HPV vaccine in historical cohorts: an immunobridging analysis of a randomised controlled trial.Lancet Glob Health. 2022; 10: e1485-e1493Summary Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 4Kreimer AR Sampson JN Porras C et al.Evaluation of durability of a single dose of the bivalent HPV vaccine: the CVT trial.J Natl Cancer Inst. 2020; 112: 1038-1046Crossref PubMed Scopus (71) Google Scholar The HPVSL pivoted to SARS-CoV-2 serology (at the request of NCI) as part of the initial pandemic response in March, 2020. Soon after, the FDA contacted NCI and HPVSL to participate in the trans-governmental network performing independent evaluation of commercial serology tests for emergency use authorisation. HPVSL developed and validated assays to characterise samples for evaluation panels to assess antibody device performance characteristics and immune response to infection and vaccination. Several evaluation panels were built, and more than 100 SARS-CoV-2 serology assays were evaluated at HPVSL, with 36 achieving emergency use authorisation by FDA and some losing emergency use authorisation status (appendix). The results from 91 of the evaluations have been published.1Pinto LA Shawar RM O'Leary B et al.A trans-governmental collaboration to independently evaluate SARS-CoV-2 serology assays.Microbiol Spectr. 2022; 10e0156421Crossref Scopus (7) Google Scholar The HPVSL also developed the first US SARS-CoV-2 serology standard, made up of large-volume, pooled, convalescent plasma samples containing IgM and IgG antibodies against SARS-CoV-2 spike and nucleocapsid and calibrated against WHO's SARS-CoV-2 international standard.5Kemp TJ Quesinberry JT Cherry J Lowy DR Pinto LA Selection, characterization, calibration, and distribution of the U.S. serology standard for anti-SARS-CoV-2 antibody detection.J Clin Microbiol. 2022; 60e0099522Crossref Scopus (2) Google Scholar This standard has been distributed to more than 170 requestors worldwide. In April, 2020, NCI received funding from the Department of Health and Human Services to develop, validate, improve, and implement serological testing and associated technologies, which was used to establish the Serological Sciences Network (SeroNet; appendix). SeroNet, which involves 25 of the top US biomedical research institutions, was tasked with expanding the USA's capacity for SARS-CoV-2 serological testing, advancing research into immune responses among diverse and clinically vulnerable populations, and researching effects of genetic and environmental factors on the immune response.6National Cancer InstituteNCI serological sciences network for COVID-19 (SeroNet).https://www.cancer.gov/research/key-initiatives/covid-19/coronavirus-research-initiatives/serological-sciences-networkDate: Nov 7, 2022Date accessed: November 11, 2022Google Scholar Capacity building centers, a key component of SeroNet, were tasked with large-volume blood sample collection to build standards, quality controls, and assay evaluation panels, and have been conducting longitudinal vaccine surveillance studies to monitor the trajectory of immune responses to SARS-CoV-2 infection and vaccination in close partnership with FNLCR. Serological research projects were funded through NCI grants and conducted by different laboratories across the USA. The Clinical and Translational Serology Task Force (CTTF) was established to address the COVID-19 pandemic through the implementation of standardised serology testing in healthy or specific patient populations, such as those with cancer or those who are immunocompromised, and to catalyse the translation of research findings into public health changes.7Lopez S Clinical and translational serology highlights: SeroNews.https://frederick.cancer.gov/initiatives/serological-sciences-network/seronews/newsletter-issue-1Date: Oct 5, 2021Date accessed: August 8, 2023Google Scholar The task force has worked extensively with academia, industry, regulatory bodies, and policy makers to address identified gaps, implement standards, identify appropriate assays for clinical and translational studies, and foster international collaborations and outreach to clinical and public health organisations (eg, WHO).7Lopez S Clinical and translational serology highlights: SeroNews.https://frederick.cancer.gov/initiatives/serological-sciences-network/seronews/newsletter-issue-1Date: Oct 5, 2021Date accessed: August 8, 2023Google Scholar In addition, the CTTF promoted public education through the publication of their newsletter, SeroNews.8Frederick National Laboratory for Cancer ResearchSeroNews.https://frederick.cancer.gov/initiatives/serological-sciences-network/seronewsDate: 2023Date accessed: August 8, 2023Google Scholar These efforts also led to the development of a real-world data infrastructure at NCI to evaluate the efficacy of vaccines and further leverage serology data from large cohorts. This infrastructure will build upon previous findings that infection rates are substantially lower in individuals with laboratory evidence of a previous infection than in people without evidence of prior infection, with risk factors including older age, immunologic conditions, and congregate care settings.9Reynolds SL Kaufman HW Meyer 3rd, WA et al.Risk of and duration of protection from SARS-CoV-2 reinfection assessed with real-world data.PLoS One. 2023; 18e0280584Crossref Scopus (1) Google Scholar The success of the trans-agency network and SeroNet showed the value of a structured collaboration for pandemic-level crises. Programmes, such as those at FNLCR, can be leveraged to manage mission-oriented networks capable of quick assay development and validation, high-quality sample collection, standards production, data acquisition and management, and high-throughput testing. An established network and infrastructure based on previous accomplishments would save time in responding to future pandemics by repurposing existing pipelines and processes. The networks established by HPVSL and NCI can serve as a precedent and model for future endeavours in the context of new outbreaks and new public health-oriented multidisciplinary initiatives (appendix). This project has been funded in whole or in part with federal funds from the National Cancer Institute and National Institutes of Health (75N91019D00024). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government. Download .pdf (.57 MB) Help with pdf files Supplementary appendix